This
study reveals key disinfection byproduct (DBP) toxicity drivers
in drinking water across the United States. DBPs, which are ubiquitous
in drinking water, form by the reaction of disinfectants, organic
matter, bromide, and iodide and are generally present at 100–1000×
higher concentrations than other contaminants. DBPs are linked to
bladder cancer, miscarriage, and birth defects in human epidemiologic
studies, but it is not known as to which DBPs are responsible. We
report the most comprehensive investigation of drinking water toxicity
to date, with measurements of extracted whole-water mammalian cell
chronic cytotoxicity, over 70 regulated and priority unregulated DBPs,
and total organic chlorine, bromine, and iodine, revealing a more
complete picture of toxicity drivers. A variety of impacted waters
were investigated, including those impacted by wastewater, agriculture,
and seawater. The results revealed that unregulated haloacetonitriles,
particularly dihaloacetonitriles, are important toxicity drivers.
In seawater-impacted water treated with chloramine, toxicity was driven
by iodinated DBPs, particularly iodoacetic acids. In chlorinated waters,
the combined total organic chlorine and bromine was highly and significantly
correlated with toxicity (r = 0.94, P < 0.01); in chloraminated waters, total organic iodine was highly
and significantly correlated with toxicity (r = 0.80, P < 0.001). These results indicate that haloacetonitriles
and iodoacetic acids should be prioritized in future research for
potential regulation consideration.